NOTCH2 as a Radioligand Therapy Target
NOTCH2, notch receptor 2, is a cell-surface protein (membrane receptor). In Human Protein Atlas immunohistochemistry, NOTCH2 staining is highest in testicular cancer (100% of samples positive), lung cancer (100% of samples positive) and melanoma (100% of samples positive). Published literature reports that NOTCH2 internalizes after ligand binding, which helps retain a radionuclide inside tumor cells. Clinical status: Clinical-stage (up to phase 2, any modality).
Is NOTCH2 a good radioligand therapy target?
Scored against the six criteria that decide whether a protein can become a radioligand therapy:
- ✅ Cell-surface accessibility: Localized to the cell surface, so a radioligand can reach it from circulation.
- ✅ Tumor expression: High IHC staining in testicular cancer, 100% of samples positive.
- ✅ Internalization: Reported to internalize, which favors radionuclide retention.
- ✅ Clinical precedent: Clinical-stage (up to phase 2, any modality)
- ❔ Shedding: Not yet assessed.
- ❔ Normal-tissue dosimetry: Check kidney, liver, bone marrow and salivary expression in the Human Protein Atlas tissue atlas.
NOTCH2 expression in cancer
Protein expression of NOTCH2 across 20 cancer types from Human Protein Atlas immunohistochemistry. The score is a weighted staining intensity from 0 to 1; "% positive" is the share of patient samples with detectable staining.
| Cancer type | IHC score | Level | % positive |
|---|---|---|---|
| Testicular Cancer | 0.64 | High | 100% |
| Lung Cancer | 0.61 | High | 100% |
| Melanoma | 0.61 | High | 100% |
| Ovarian Cancer | 0.58 | High | 100% |
| Thyroid Cancer | 0.56 | High | 100% |
| Prostate Cancer | 0.56 | High | 100% |
| Skin Cancer | 0.55 | High | 100% |
| Bladder Cancer | 0.53 | High | 92% |
| Cervical Cancer | 0.50 | Medium | 100% |
| Pancreatic Cancer | 0.48 | Medium | 91% |
| Breast Cancer | 0.47 | Medium | 92% |
| Gastric Cancer | 0.42 | Medium | 82% |
| Endometrial Cancer | 0.42 | Medium | 75% |
| Colorectal Cancer | 0.36 | Medium | 83% |
| Head and Neck Cancer | 0.33 | Medium | 75% |
| Neuroendocrine Tumors | 0.33 | Medium | 75% |
| Glioma | 0.30 | Medium | 70% |
| Liver Cancer | 0.27 | Medium | 55% |
| Lymphoma | 0.13 | Low | 30% |
| Kidney Cancer | 0.09 | Low | 18% |
Is NOTCH2 internalized?
Yes. Notch ligands bind these EVs on the neuronal plasma membrane, trigger their internalization, activate the Notch signaling pathway, and drive the expression of Notch target genes.
Sources: PMID 38241148 · PMID 38016980 · PMID 26288744. AI-extracted from abstracts, so verify before citing.
NOTCH2 clinical trials
Clinical-stage (up to phase 2, any modality). Nuclens hasn't indexed trials for NOTCH2 yet. Search ClinicalTrials.gov for NOTCH2 trials.
NOTCH2 normal tissue expression
Normal-tissue expression in dose-limiting organs (kidney, liver, bone marrow, salivary glands) drives radioligand dosimetry risk. Nuclens is re-validating its normal-tissue values, so they are not shown here yet. See NOTCH2 in the Human Protein Atlas tissue atlas, and read how normal-tissue expression predicts radioligand dosimetry risk.
NOTCH2 gene essentiality (DepMap)
CRISPR knockout effect across 1258 cancer cell lines: -0.05 (not essential). Radioligands kill by radiation, not by blocking the target, so essentiality matters less than for inhibitors. A non-essential target can still be an excellent radioligand target.
Related testicular cancer radioligand targets
HER3 (ERBB3) · c-MET (MET) · STEAP2 · KIT · SSTR2 · TMEFF2 · Mesothelin (MSLN) · HER2 (ERBB2)
See all radioligand therapy targets in testicular cancer.
See how NOTCH2 ranks against 15,000 targets for your indication.
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Subcellular localization: UniProt via Open Targets (CC BY 4.0 / CC0). Tumor immunohistochemistry: Human Protein Atlas (CC BY-SA 4.0). Clinical trials: ClinicalTrials.gov (public domain). Gene essentiality: DepMap (CC BY 4.0). Internalization and shedding: AI-extracted from PubMed abstracts, so verify against the cited papers before relying on them. Nuclens is a first-pass triage layer, not a substitute for wet-lab validation or clinical dosimetry. Derived expression data on this page is shared under CC BY-SA 4.0.